The objectives of this research are to elucidate all the components and processes that are involved in the uptake/efflux, storage, mobilization and utilization of copper within cells. A parallel objective is to determine the molecular basis of Menkes steely-hair syndrome and Wilson's disease which are diseases of copper metabolism. The cellular systems that will be examined are isolate hepatocytes, isolated intestinal villus cells, renal cells, erythrocytes, erythrocyte ghosts, fungal cells and yeast cells. The mouse brindled mutant of the X-chromosome will be one of the cell sources as an animal model for Menkes disease. Bedlington terriers serve as a putative animal model for Wilson's disease. In each system, the kinetics of uptake/efflux will be analyzed by the conceptual tools of standard enzyme kinetics. Each subcellular fraction in each cell type will be carefully evaluated in metabolic pathway experiments aimed at elucidating the order of steps which leads to copper incorporation into essential cooper proteins. We will attempt to identify as many cellular copper components as possible in the particulate fractions. Low molecular weight, mobilization-utilization factors will also be searched for. Erythrocytes and erythrocyte ghosts will be used to determine the role of specific membrane proteins in zinc and copper uptake. Particulary in the microorganism systems, the role of copper and manganese in the regulation of the protein synthesis of superoxide dismutases will be examined carefully.